Nouveaux médicaments anti-inflammatoires.

摘要

Novel compounds of formula in which R1 is a phenyl or 5- or 6-membered heteroaromatic monocyclic radical that is unsubstituted or has from 1-3 substituents; R2 is a hydrogen atom, or a C1- 5 alkyl, aryl, or aralkyl radical which may be substituted by one or more alkoxy, halo, amino, substituted amino or nitro radicals, or is a C2- 5 alkenyl, cycloaliphatic or alkanyl radical; R3 is a halogenated methylene radical; R4 is hydroxy, amino, substituted amino, C1- 5 alkoxy, aralkoxy or -OM radical, M being a cation; R5 is a hydrogen or halogen atom, or a C1- 5 alkyl C1- 5 alkoxy, haloalkyl, nitro, amino, substituted amino, aryl, aryloxy, hydroxy, mercapto, sulphamoyl, sulphoxide, carboxy, carboalkoxy, cyano, aminomethyl, alkyl-substituted aminomethyl, dialkylsulphamoyl, or benzylmercapto radical; and R6 is a hydrogen atom or a C1- 5 alkyl or C2- 5 alkenyl radical; and the anhydride derivatives of the acids; are prepared by treating an indole of formula in which R1 is an alkyl or aralkyl group with a halogenated triphenyl phosphorane of formula (C6H5)3P = R13, and, if desired, hydrolysing the ester formed (R4 is alkoxy or aralkoxy) to the corresponding acid (R4 is hydroxy), which may be converted to a symmetrical or mixed anhydride which is reacted with ammonia, a primary or secondary amine, or an alkanol or aralkanol in the presence of a non-hydroxylic base to give the corresponding amide, substituted amide or ester of Formula (I) (R4 is amino, substituted amino, alkoxy or aralkoxy), or which may be esterified with an alkanol or aralkanol to produce the corresponding ester. The 3-keto ester indole of Formula (II) may be prepared by reacting an oxalyl halide with the N-1 unsubstituted indole to give a 3-indole glyoxalyl halide which is then reacted with an alkanol or aralkanol to yield the alkyl or aralkyl 3-indoleglyoxalate the aralklyation or heteroaralkylation of which gives the N-1 aralkylated or hetero-aralkylated 3-keto ester indole of Formula (II). The foregoing steps may be reversed, i.e. the indole may first be aralkylated in the N-1 position, followed by introduction of the 3-keto ester residue. Therapeutic compositions having anti-inflammatory and antipyretic activity, which may be administered, e.g. orally, contain as active ingredients compounds of Formula (I) above.